Effect of Glucocorticoids on Glycosaminoglycan Metabolism in Cultured Human Skin Fibroblasts

Särnstrand, Bengt; Brattsand, Ralph; Malmström, Anders

doi:10.1111/1523-1747.ep12530360

Cited by 44 publications

(25 citation statements)

References 24 publications

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“…The immediate-onset skin thinning in duced by CS is due to the fact that the formation of ground substance of the connective tissue -like hyaluronic acidis inhibited [10,11 ]. Katz et al [12] proposed to call this phenomenon preatrophy.…”

Section: Discussionmentioning

confidence: 99%

Skin Atrophy Induced by Initial Continuous Topical Application of Clobetasol Followed by Intermittent Application

Lubach¹,

Rath²,

Kietzmann

1995

Dermatology

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Background: The most frequent side effect of a long-term topical corticosteroid therapy is skin atrophy. To avoid or to reduce atrophy often an initial continuous application is followed by an intermittent maintenance therapy. Objective: In this study we measured the skin thickness before and after the two-phase application schedule with the superpotent topical steroid clobetasol propionate (CP). For 16 days CP samples were applied twice daily on the test areas of 12 volunteers (phase 1). Then CP was applied to the same skin areas in accordance with the following timing: every 5th day, every 7th day, every 10th day, every 14th day (phase 2). Phase 2 lasted for 45 days. During the entire period of the study the skin thickness was measured regularly by the skin compression and thickness method as described previously. Results: It could be seen that in phase 1 the skin became about 15% thinner. In phase 2 the steroid-induced skin thinning was approximately the same when CP was applied every 5th or 7th day. The skin thickness reached a more or less normal level when CP was applied every 10th day. After the 14th day a completely normal level was found. By measuring the skin thickness every day it was further shown that the skin thinning process lasted for 3 days when CP was applied once only. Conclusion: These results demonstrate that skin thinning must be expected by an intermittent maintenance therapy applied at relatively short intervals. The longer the intervals, the weaker the skin thinning. Moreover, these investigations showed that the skin thinning effect after a single CP application persists for nearly 3 days.

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Section: Discussionmentioning

confidence: 99%

Skin Atrophy Induced by Initial Continuous Topical Application of Clobetasol Followed by Intermittent Application

Lubach¹,

Rath²,

Kietzmann

1995

Dermatology

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“…The basis of this phenomenon has been inten sively investigated in recent years [2][3][4][5], It is well established that glucocorticoids can inhibit cell proliferation and mitosis [6], decrease collagen [7] and glycosaminoglycan synthesis [8], and general protein production. There is consensus that glucocorticoids direct ly influence the metabolism of dermal fibro blasts.…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of Medium Potent Nonhalogenated Double-Ester-Type and Conventional Glucocorticoids on Proliferation and Chemotaxis of Fibroblasts in vitro

Hein

Körting²,

Mehring³

1994

Skin Pharmacol Physiol

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Recently several attempts have been made to develop glucocorticoids which show less pronounced side effects. We intended, therefore, to use experimental systems to examine the influence of newly developed nonhalogenated glucocorticoids and conventional fluorinated congeners, demonstrating similar anti-inflammatory activity in vivo, on biosynthetic capacities of human fibroblasts. Fibroblasts were kept in monolayer cultures and exposed to different concentrations of the active compounds for 6 days to analyze the influence on proliferation. Chemotaxis of fibroblasts was studied in blind well Boyden chambers. Fibroblast-conditioned medium was used as chemoattractant. All glucocorticoids tested influenced fi-broblast proliferation at high (10^-5M) and low (10^-9M) concentration. Yet the effect was clearly more marked with fluorinated compounds. Basically, the same applied for chemotaxis. At the low concentration, however, nonfluorinated glucocorticoids exerted almost no influence. These results suggest that modifications of steroidal structure can specifically influence their effects on biosynthetic capacities of fibroblasts.

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“…Sarnstrand et al (23) reported that glucocorticoid treatment not only reduced the quantity of various glycosaminoglycans but also changed the distribution, relative proportion, and structure of connective tissue proteoglycans. These changes may contribute to hyalinization of dermal collagen bundles, which is marked at the sites treated with potent corticosteroids.…”

Section: Histologic Changesmentioning

confidence: 99%

Dorsal Skin Reactions of Hairless Dogs to Topical Treatment with Corticosteroids

Kimura

Doi

1999

Toxicol Pathol

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Dorsal skin reactions to continuous topical treatment with different types of corticosteroids were histologically investigated in hairless descendants of Mexican hairless dogs. The preparations tested were prednisolone (ST-1; weak), fluocinolone acetonide (ST-2; moderate), diflucortolone valrerate (ST-3; strong), and mometasone furoate (ST-4; very strong). Grossly, the sites treated with ST-3 and ST-4 showed moderate inflammatory reactions. After completion of the corticosteroid treatment, both sites were less pigmented and had a thin texture. The severity of histologic changes in the skin was dependent on the efficacy of the corticosteroids. The epidermis was prominently thinned from 1 wk after treatment with the corticosteroids, resulting in a flat dermis-epidermis junction. By the end of the corticosteroid treatment, these lesions became progressively more severe. At 2 wk after completion of topical treatment, the epidermal thickness in the sites treated with ST-1 and ST-2 began to return to normal values, whereas the epidermis of the skin treated with ST-3 and ST-4 became thinner. At 3-4 wk after topical treatment with ST-3 and ST-4, the dermis showed hyalinization of collagen bundles. These dermatologic findings in hairless dogs are in accordance with steroid-induced skin atrophy of human beings. These results suggest that the skin of hairless dogs responds sensitively to topical corticosteroids and that these animals are a useful model for investigating the efficacy and adverse effects of cutaneous topical corticosteroids.

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Effect of Glucocorticoids on Glycosaminoglycan Metabolism in Cultured Human Skin Fibroblasts

Cited by 44 publications

References 24 publications

Skin Atrophy Induced by Initial Continuous Topical Application of Clobetasol Followed by Intermittent Application

Skin Atrophy Induced by Initial Continuous Topical Application of Clobetasol Followed by Intermittent Application

Differential Effect of Medium Potent Nonhalogenated Double-Ester-Type and Conventional Glucocorticoids on Proliferation and Chemotaxis of Fibroblasts in vitro

Dorsal Skin Reactions of Hairless Dogs to Topical Treatment with Corticosteroids

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